Faculty Collaboration Database

Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies. Antimicrob Agents Chemother 2015 Aug;59(8):4424-8

Date

05/20/2015

Pubmed ID

25987632

Pubmed Central ID

PMC4505228

DOI

10.1128/AAC.00581-15

Scopus ID

2-s2.0-84939863729 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.

Author List

Cumpston A, Caddell R, Shillingburg A, Lu X, Wen S, Hamadani M, Craig M, Kanate AS

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Antibiotic Prophylaxis
Antifungal Agents
Chemistry, Pharmaceutical
Delayed-Action Preparations
Female
Hematologic Neoplasms
Humans
Male
Middle Aged
Mycoses
Suspensions
Tablets
Triazoles
Young Adult